Great. Good afternoon, everyone. My name is Ted Tomas. I'm a senior biotech analyst at Piper Sandler. And before I begin, I am required to point out certain disclosures regarding Piper and our next presenting company, CytomX, which are located at the back of the room on the placard there and also at the registration desk. So CytomX was my single best-performing stock in 2025. Thank you. Congratulations. That's pretty cool to see. The company's proprietary Probody technology masks proteins and antibodies from binding to target tissue or to targets on healthy tissue to really increase the therapeutic window. And what we got this year was some encouraging phase one data on CX-2051 and colorectal cancer that honestly validated this approach.
They also just recently showed that this can work in more than just antibodies and showed some really compelling early phase one data on an Interferon alpha-2b CX801 at SITC. So a lot of really cool stuff going on here. What I always like talking to Sean about is, where do you go from here? Because you've got a huge opportunity with 2051, but then really the sky's the limit in terms of where you take this technology. So please introduce Chairman and CEO Sean McCarthy. Sean, thanks for being with us. Maybe you can start off by describing this Probody technology because I kind of did a hack job at it. But how does it work and what are the advantages of masking these therapeutic proteins?
Yeah, thanks, Ted. It's a pleasure to be here. Thanks for having us at the conference. And obviously, we're delighted to have been your number one performer in 2025. It's been quite a year for us. So beginning with the technology, the platform technology, which we call the Probody therapeutic platform. This is a very innovative biologic masking strategy that we have pioneered at the company. In fact, I refer to CytomX as the original masking company. We've really led the field now for more than a decade. And the basic concept is to take a therapeutic protein, whether it's an antibody or a cytokine, T cell engager or ADC, and to mask the biologic in a way that diminishes binding in normal tissues to target in normal tissues, but opens up binding in tumor tissue by virtue of cleavage of the mask by tumor-associated proteases.
So we've known for decades, and I'm a cancer biologist by background. We've known for a very long time that tumor tissue has high levels of proteases. And that's because tumor cells are, from their very transformation, beginning to invade, migrate, and metastasize. And that involves proteolytic events. We take these proteases and we use them, leverage them to clip off the mask in a specific and selective way. And this allows for a fundamentally different distribution of active drug in patients and allows us to do some really incredible things, going after targets that are very abundant in the tumor, regardless of whether they're present on normal tissues. And the two programs that we're currently in the clinic with are masked anti-EpCAM ADC that you mentioned, CX2051, and our masked interferon alpha are both CX801, we think, really excellent examples of how to use masking technology.
And they also build on more than a decade of experience at CytomX. Of course, we like to say in biotech, there's no such thing as an overnight success, but we truly have had a breakthrough year in 2025.
I think 2051 is almost an ideal application in EpCAM antibody-drug conjugate. Why is EpCAM such a good target for an ADC to mask?
EpCAM is a very abundant tumor antigen in colorectal cancer and also in many other tumors. In fact, it was first identified a long time ago in 1979. It's been of interest to drug developers for decades, given its high level of expression in tumor tissue, and particularly in CRC. One of the biggest challenges with EpCAM, however, is that it's present on most normal tissues. EpCAM stands for epithelial cell adhesion molecule. It's present at high levels on many normal tissues. That's presented roadblocks to development of therapeutic strategies against EpCAM. Specifically, some of the early approaches to targeting EpCAM ran into toxicity roadblocks very early in clinical development, specifically pancreatitis, liver toxicity, to name just two. It's been really a challenging target to open a therapeutic window for. We've had a long-standing interest in EpCAM.
It goes back to work that we've been doing with ImmunoGen, now of course part of AbbVie. I think going back some years, asking the question if we could make a masked antibody drug conjugate to EpCAM, maybe we could truly break through in delivering a systemic therapy. I should also note that one of the clues that really led to, I think, our success with this systemic drug is that we do know that if you locally target EpCAM, it can be quite effective in shrinking tumors. But these local strategies have had to be pursued because systemic strategies have been too toxic. So what we're doing with 2051 is opening a therapeutic window for the first time for an ADC against EpCAM with an initial laser focus in development in colorectal.
Sean, with that, walk us through the phase 1 CX-2051 data you guys reported in metastatic colorectal cancer this year, both from a safety and efficacy standpoint. Because again, as you're outlining, EpCAM is a well-validated target, but you couldn't do it safely. You guys really kind of checked both boxes here.
Yeah, we've made terrific progress in the first year and a half in the clinic. And we began our dose escalation in Q2 of 2024. And just one year later, in May of this year, we presented our first look at the dose escalation results from about 25 patients in the safety database, 18 efficacy evaluable patients. And it really was a tremendously exciting moment for the company to share this data. So the phase one study that we did, I should also really emphasize that we decided to be very focused only in colorectal. It's more typical to do, of course, a broad signal-seeking study with a target like this or a drug like this. But we've really felt that the CRC experiment was the right one to do first. And therefore, every patient that we enrolled in dose escalation was a late-stage metastatic CRC patient.
The results, first of all, on the safety side of things, drugs well tolerated. This is a Topoisomerase I payload. We saw toxicities that are consistent with topo I inhibition, fairly low rates of hematologic toxicity, some level of GI toxicity in the form of upper GI nausea, vomiting, lower GI diarrhea. And we continue to monitor and understand that profile as we move forward. On the efficacy side of things, tremendously exciting. We saw out of 18 efficacy evaluable patients, a confirmed response rate of 28%. And to put that in context, in the late line, our patients had a number of prior therapies of median of four priors. So this is essentially a fifth line or later patient population. And the benchmark for third line plus response rates is in the single digits with current standard of care.
So we've really moved the needle, seeing deep and durable responses in this very difficult to treat patient population. And I think we can conclude from this initial dataset that also delivered 5.8 months of progression-free survival and 94% disease control, that this drug is working exactly as we designed it, and we just think has enormous potential in CRC.
Yeah, very exciting. Now, this was just the interim look. So we will get some more data early next year. Tell us what to expect from that. And then sort of how do you envision developing CX-2051?
At the time of our data disclosure in May, we had already decided to expand three dose levels, 7.2, 8.6, and 10 mg per kg. The drug is given on a Q3 week schedule. That expansion has gone very well. We announced in August that we had already met our enrollment goal of increasing enrollment at each of those dose levels to about 20 patients. And in fact, we announced on our earnings call a couple of weeks ago that we have decided to add additional patients during Q4 and into Q1 next year to increase enrollment to about 100 patients in the phase one study. We're on track to give an update on the 2051 study in Q1 of next year. That will be across those three expansion dose levels.
Updates, of course, on the efficacy that we're seeing on the safety profile, including some efforts that we've been taking to use prophylactic measures to get ahead of some of the GI toxicities to further expand therapeutic window. I also anticipate that in this Q1 update, we'll have an initial look at progression-free survival at each of these three dose levels, which will be really important in terms of setting up dose selection for the next study. In terms of what that next study could look like, the absolute top priority for our company right now is to get 2051 on the path to registration as a monotherapy. We want to get this drug to the market. We want to get it into oncologists' hands. We think it could be a very important addition to the landscape. There are a number of ways we could go here.
We haven't locked into any specific strategy yet, but for example, we could run a fourth line study randomizing against standard of care in the fourth line, something like fruquintinib. That's a study we think could execute very, very quickly with most likely a primary endpoint of progression-free survival, which is why I was emphasizing PFS in this next update coming in Q1. We're also very interested in the third line. The 5.8-month preliminary PFS assessment that we reported in May is very encouraging and we think could be competitive. We need to learn more about monotherapy over time to see how it could stack up against standard of care in the third line, which is Bev, bevacizumab, and Lonsurf, which has a PFS of about 5.7 months and an ORR of about 5%-6%.
So a little bit more work to do there to look at this expansion dataset at monotherapy to figure out what a potential third line strategy could be, either for monotherapy or potentially for a combination with bevacizumab. With that in mind, we also announced on our earnings call recently that we are initiating the Bev combination in Q1 of next year to begin to set the stage for bringing the drug into earlier and earlier lines of therapy, and of course, although as is standard, we're initially focused in the late line in CRC, our vision for 2051 is and has always been that it has potential to replace irinotecan in CRC therapy in the earlier lines and perhaps over time even replace chemotherapy altogether.
So we see a terrific and very broad opportunity and a multi-layered long-term development program for 2051 with the key goal in the near term of getting the monotherapy onto a registrational path.
Is this something CytomX can do themselves, or is this something that you think would require a partner to get to the earlier lines and maybe even cancers beyond colorectal?
So certainly in the context of our late line registrational pathway and thinking there, we absolutely have the ability and the resources to go all the way ourselves. And obviously for a company of our size and shape in the public market, I think that's a very compelling opportunity for investors, I would say. Looking to the longer term, given the breadth of the program, not just in CRC, and Ted, as you allude to, EpCAM is present on just about every other solid tumor. So now that we know we have an active drug and in a way we've done the hardest experiment first in colorectal, we're highly motivated to expand into other tumor types. So you can see this program getting very big, very quickly, and we want to maintain urgency. We want to maintain speed. And so a partnership at the right time could make some sense.
As I've said many times in firesides like this, we like doing business development. We've got a strong history and track record of doing business development and doing transformational deals. With this, like every other program and the platform, we'll do the right deal at the right time.
Great. I'm just going to pause there and see if there are any questions from the audience on 2051 before we kind of keep moving into 801 and also even earlier into the pipeline. So you guys just presented some early phase one data on your masked interferon alpha-2b, CX801 in melanoma, including clean safety data. And also what I thought was some very compelling biomarker data. So took a little bit of paying attention to see what you guys really were talking about here. But walk us through what you saw and what that really means in terms of developing this compound and what are next steps for 801?
So really excited about 801 as a drug candidate. We tend to think of it as our second child, and our second child is growing up fast. There's been a lot of attention on 2051, understandably. But 801 is, in a way, has some similarities to the EpCAM program in that interferon alpha, and specifically interferon alpha-2b, is a cytokine that's been known for a long time. It was the first immunotherapy to be approved decades ago. It's known to have single-agent anti-tumor activity. It is a very powerful multimodality multimode modulator of the immune microenvironment. But it's been a challenging drug to use as a monotherapy because it has severe systemic toxicities. So we reasoned that we could leverage our masking strategy to improve the systemic tolerability of interferon alpha whilst capturing, or if you like, unleashing its intra-tumoral immunobiology by masking.
The concept is the drug will be masked in the periphery and therefore quiescent in the tumor. The mask, dual masks actually, will be removed, allowing the interferon to modulate various immune cell populations and setting the stage for essentially turning cold tumors hot. The data that we shared at SITC is a really great start. We believe it's our first five patients treated with monotherapy CX801 in late-stage melanoma, a dose escalation study. We have paired biopsies from all five of those patients. The poster that we presented shows, and there's a lot of science in the poster. It's quite a fair amount to digest. But what it essentially shows, there's some really beautiful images there looking at single cells, spatial gene regulation kinetics and such like. What the data essentially shows is this drug is working exactly as we designed it.
We're seeing activation in the tumor microenvironment of interferon responsive genes in multiple cell populations, in the melanoma cells themselves, in stromal cells, in different immune cell populations, and also in vascular cells. So this really underscores one of the real benefits of using the interferon mechanism, which is that it functions across so many cell populations in the tumor microenvironment. We also have seen really powerful recruitment of T cells, CD8 positive T cells into the tumor microenvironment, which is exactly what we want to see to, again, drive that inflammatory phenotype. And then thirdly, we've been able to measure induction of checkpoint genes, specifically PD-1, PD-L1, and LAG-3, which are in and of themselves interferon responsive. The reason that's particularly important is that that sets the stage for the combination with Keytruda. We have access to Keytruda through our collaboration and supply agreement with Merck.
And we began treatment of melanoma patients with Keytruda in combination with 801 earlier this year. And the therapeutic concept is activate the immune system with 801. Interferon tends to overshoot by inducing these checkpoint proteins. So then we can come back in with Keytruda, release that brake, and we hope restore checkpoint sensitivity to late-stage melanoma. So that's the experiment we'll be doing between now and late 2026. And we'll be really excited to share our combination data in melanoma later next year.
Great. Very, very exciting. And again, I really do appreciate the parallels between EpCAM and interferon 2B. Now, also at SITC, you guys presented preclinical data on CX908, which is a dual masked T cell engager targeting P-cadherin and CD3. Tell us about this program. And is this a potential future molecule that you guys would develop?
So yeah, our work in T-cell engagers continues, although we've become, with our clinical programs, we're very focused on the ADC with 2051. We do see ADCs as an absolute killer application of masking technology. But we've been in the T-cell engager space for quite some time as well. And we have quite a bit of experience, including the clinical development of these assets, which I might say is not straightforward. It can be a little challenging. But the promise of T-cell engagers in solid tumors is immense. And we really do think that masking is a way to unlock their potential in the solid tumor context. So we are working with several collaborators in this space with Regeneron and Astellas and Bristol Myers.
So the majority of the work that we've been doing in T cell engagers is in the context of those partnerships as we continue to learn and optimize the technology and the strategies. But yeah, very excited to have shared a new program that's CX908 targeting P-cadherin. P-cadherin is another name for this target. And we presented preclinical results showing activity in lung tumor models, in breast cancer models, and a very wide broadening of therapeutic window by masking on both the P-cadherin and the CD3 arms. So the strategy is to bring this molecule into multiple solid tumors by opening therapeutic window and masking, of course, on the tumor antigen to minimize on-target toxicities, masking on the CD3 arm to minimize the immune toxicities and particularly CRS.
We feel pretty confident about that because of an earlier program we developed a few years ago, CX904, which was our EGFR CD3, where we showed that masking had a profound impact in reducing CRS in patients. We're excited about 908. To your question about further development or partnering, we do see it as an asset that could absolutely benefit from a partner. We do think the T cell engager space in general continues to make sense to be a partnered program for us. We'll see what 2026 brings.
Now, you mentioned some of the partnerships that you have. You guys have been successful, prolific. It's brought in non-dilutive funding. With so much going on in the clinic right now and on the proprietary work, do you still envision doing discovery partnerships or partnerships kind of the original flavor that you guys did? Or is it really more about productization at this point?
Great question. And in a way, it brings us all the way back to the beginning of the discussion today because I agree with you, and I think many others agree with you too, that the data that we've shared so far on CX2051, the EpCAM ADC, really is the most definitive proof of concept so far for the CytomX Probody platform. And that's just really exciting. I mean, we hear that all the time. And that does translate into, I think, potential for additional platform partnerships again in the future. I mean, we took a little bit of a break over the last couple of years while we navigated many things, including a very challenging macro environment. And we really stayed laser-focused on getting 2051 to this important proof point. But I'd say, yeah, we're absolutely open for business on the discovery side.
Given that the Probody platform has such application across so many modalities, I think that there's room for additional partnerships for sure.
And the entry fee just went up with this all.
The entry fee went up, but we also, of course, recently recruited a terrific new addition to the team, Rachel Lester, who joined us as Chief Business Officer and has really hit the ground running. It's just so exciting to have her and her really deep, broad-based strategic and BD experience helping to spearhead some of these conversations.
She's a dynamo. That's a great addition. So you guys ended the third quarter with $144 million in cash. I think you subsequently took down some more on the ATM, so maybe up over $150 million-$158 million, I don't know. How long does this fund the company? And what does it really enable you to accomplish?
Yeah, so we're in a robust cash position, comfortably funded into Q2 2027. That certainly puts us in a position to get to this next data set, initiate the next clinical study for CX2051, begin the combination with bevacizumab, and continue the dose escalation of CX801 with Keytruda in melanoma. So really in an excellent position. Finishing 2025, that has been, it really has been a transformational year for the company. We're finishing the year very strong and really excited about what 2026 can bring. And once again, I want to thank you for having us today and for your guys' support.
My pleasure. And I'm looking forward to an exciting 2026. No pressure.
Thanks, Ted.
Thanks, buddy.